Metastatic Melanoma
Conditions
Keywords
Metastatic Melanoma, Everolimus, RAD001, Bevacizumab
Brief summary
This is a non-randomized, open label Phase II study comparing bevacizumab and everolimus in the treatment of metastatic melanoma.
Detailed description
All patients will begin treatment with the same doses of RAD001 and bevacizumab. Patients will receive 6 weeks of treatment, followed by re evaluation. Patients with objective response or stable disease will continue treatment until disease progression. During the study, all patients will receive 10 mg of RAD001 orally daily and 15 mg/kg of bevacizumab intravenously (IV) once every 3 weeks. Fifty-five patients will be enrolled in this multi-centered study
Interventions
DRUGBevacizumab
15 mg/kg of bevacizumab intravenously (IV) once every 3 weeks.
DRUGEverolimus
10 mg by mouth daily
Sponsors
Genentech, Inc.
Novartis
SCRI Development Innovations, LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Histologically confirmed melanoma. 2. Unresectable stage IV disease, or recurrent disease with metastases. 3. Measurable disease (by Response Evaluation Criteria in Solid Tumors \[RECIST\]) or measurable skin lesions. 4. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2. 5. Life expectancy \>=12 weeks. 6. Patients are allowed 0-2 prior treatment regimens containing chemotherapy and/or immunotherapy (interferon, interleukin 2). 7. Women of childbearing potential must have a negative serum pregnancy test with 7 days before beginning treatment. 8. Absolute neutrophil count (ANC) \>=1500/µL, and platelets \>=100,000/µL. 9. Serum creatinine \<=2.0 mg/dL. 10. Serum bilirubin \<=1.5 mg/dL institutional upper limit of normal (ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \<2.5 × ULN or \<5 × ULN in patients with documented liver metastases.
Exclusion criteria
1. Previous treatment with bevacizumab or other anti-angiogenesis agents. 2. Previous treatment with mTOR inhibitors. 3. Drugs or substances known to be inhibitors or inducers of the isoenzyme CYP3A are not allowed. 4. Treatment with investigational agents within 4 weeks of study entry. 5. Treatment with more than two previous chemotherapy regimens. 6. Immunization with attenuated live vaccines within one week of study or anytime during study treatment period. 7. Female patients who are pregnant or breastfeeding. 8. Central nervous system (CNS) involvement by metastatic melanoma. 9. CNS disease (e.g., seizures not controlled with standard medical therapy, history of stroke). 10. Any severe and/or uncontrolled medical conditions or other conditions that could affect participation in the study such as: * Severely impaired lung function. * Uncontrolled diabetes as defined by fasting serum glucose \>1.5 ULN, * Any acute or chronic uncontrolled infection/disorder. * Non-malignant medical illnesses that are uncontrolled or whose control may be jeopardize by the treatment with the study therapy. * Any acute or chronic uncontrolled infection/disorder. * Non-malignant medical illnesses that are uncontrolled or whose control may be jeopardize by the treatment with the study therapy. * Liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis. 11. Acute myocardial infarction (MI) with the previous 6 months. 12. Clinically significant cardiovascular disease (e.g., uncontrolled hypertension, unstable angina, New York Heart Association \[NYHA\] Class II or greater congestive heart failure \[CHF\], serious cardiac arrhythmia requiring medication), or \>= grade 2 vascular disease. 13. Clinical history of hemoptysis or hematemesis. 14. Clinical evidence or history of a bleeding diathesis or coagulopathy. 15. Major surgical procedures, fine-needle aspirations, or core biopsies with 7 days of starting treatment. 16. Patients with PEG tubes or G-tubes. 17. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of RAD001 (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection). 18. Proteinuria at screening as demonstrated by either 1. Urine protein:creatinine (UPC) ratio \>= 1.0 at screening OR 2. Urine dipstick for proteinuria \>= 2+ (patients discovered to have \>=2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate \<= 1g of protein in 24 hours to be eligible).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | 13 months | Length of time, in months, that patients were alive from their first date of protocol treatment until worsening of their disease |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival Rate | 1 year | Overall Survival is defined as the length of time, in months, that patients were alive from their first date of protocol treatment until death. For patients who were alive at the time of calculation, follow-up time was censored at date of last contact. The percentage of patients who were alive at 1 year is reported here. This was estimated using the Kaplan Meier method. |
| Objective Response Rate (ORR) | 13 months | The percentage of patients who experience an objective benefit from treatment (CR+PR). The response categories were assigned using RECIST criteria. Complete Response (CR) = Disappearance of all target lesions ; Partial Response (PR) = \>=30% decrease in the sum of the longest diameter of target lesions. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Intervention All patients received bevacizumab 15 mg/kg, administered by intravenous (IV) infusion on day 1 of each 21 day course. In addition, patients received everolimus 10 mg orally on a daily basis. | 57 |
| Total | 57 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 5 |
| Overall Study | Intercurrent Illness | 8 |
| Overall Study | Lack of Efficacy | 35 |
| Overall Study | Physician Decision | 5 |
Baseline characteristics
| Characteristic | Intervention |
|---|---|
| Age, Continuous | 70 years |
| Region of Enrollment United States | 57 participants |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 56 / 57 |
| serious Total, serious adverse events | 29 / 57 |
Outcome results
Primary
Progression-free Survival
Length of time, in months, that patients were alive from their first date of protocol treatment until worsening of their disease
Time frame: 13 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Intervention | Progression-free Survival | 4 months |
Secondary
Objective Response Rate (ORR)
The percentage of patients who experience an objective benefit from treatment (CR+PR). The response categories were assigned using RECIST criteria. Complete Response (CR) = Disappearance of all target lesions ; Partial Response (PR) = \>=30% decrease in the sum of the longest diameter of target lesions.
Time frame: 13 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention | Objective Response Rate (ORR) | 7 Participants |
Secondary
Overall Survival Rate
Overall Survival is defined as the length of time, in months, that patients were alive from their first date of protocol treatment until death. For patients who were alive at the time of calculation, follow-up time was censored at date of last contact. The percentage of patients who were alive at 1 year is reported here. This was estimated using the Kaplan Meier method.
Time frame: 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intervention | Overall Survival Rate | 43 percentage of participants |